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The Expanding Vaccine Market – Pharmpro

Vaccines continue to be one of the brighter spots for pharmaceutical companies in the current market, and revenues for vaccine products are expected to continue their double-digit growth in the future. Driving that growth is an increasing acceptance of adult vaccines and the public health focus on flu prevention, as well as introductions of new vaccines. Improved production techniques will also play a role in enabling the products to come to market.

The Market for Vaccines

The vaccine market is generally separated into two segments: pediatric and adult. Pediatric is larger but adult vaccine revenues have grown faster. Kalorama Information estimates that world sales of adult vaccines reached $12.5B in 2010, up from $10.1B in 2009 largely on strong growth of influenza vaccines. Sales of adult vaccines are projected to increase at a compound annual rate of 10.3% from 2010 to 2015. World sales of pediatric vaccines exceeded $12.7B in 2010, increasing 10.1% over 2009 sales of $11.5B on rising sales of combination, varicella and other products. Sales of pediatric vaccines are projected to increase at a compound annual rate of 8.4% from 2010 to 2015.

Most vaccine revenues are earned by five companies: Sanofi Pasteur, GlaxoSmithKline, Merck & Co., Pfizer, and Novartis. They held nearly 80% of the market as of 2010. All of these companies have seen growth in their vaccine business. In 2010, Sanofi Aventis subsidiary Sanofi Pasteur was the leading manufacturer with 22.2% share and more than $5.6B in sales. The company’s position was largely due to its influenza products, although its polio/pertussis/Hib products also account for a significant portion of its vaccine sales. GlaxoSmithKline followed.

World Market for Vaccines by Type 2006-2015. Source: Kalorama Information

New Products and Production TechniquesIt’s not likely that the vaccine market will be limited to the products on the market today. Most companies have increased their R&D programs in this area in recent years. Kalorama Information has estimated a $10B market potential in the next six years for vaccines currently in Phase III. Diabetes, allergies, dengue fever, herpes and malaria are among the conditions for which there is a need and a vaccine in late-stage development.

These vaccines can only impact public health and pharmaceutical businesses if they can reach the market. To meet the demand for vaccines, production techniques are an important but overlooked area of vaccine development. Improvements in production methods can significantly impact both speed to market and cost. At present, many vaccines, such as flu vaccine, are grown in chicken eggs. Although it has been reliably used for more than 60 years, this technique is slow and expensive. With roughly a 6 month lead time from final sequencing of the seasonal/pandemic virus to production, the virus has already done significant damage. Furthermore, initial investment in production can reach $150M or more. This technique can also raise issues of allergic reactions to egg proteins and biosafety concerns.

Certain plants, particularly tobacco, have shown promise as they have been extensively researched, are inexpensive to grow and can yield very large amounts of vaccine quickly. In this process, proteins from the H1N1 virus known to trigger a protective immune response in a patient, without causing an infection, are isolated. A gene for this protein is then introduced into a bacterium. Tobacco plants are exposed to the bacteria, which causes the plants to become infected with the gene-carrying bacteria. The infected plants then begin to produce the protein from H1N1 in large quantities. After about a week of growth, the leaves of the plants are harvested and crushed so that the H1N1 protein, which becomes the basis of the vaccine, can be extracted and purified. In 2010, Medicago reported positive results for a tobacco-based H5N1 vaccine and announced an agreement with PT BIO FARMA to build a plant-based vaccine manufacturing facility in Indonesia which could potentially supply the global market. The company has also signed agreements with vaccine producers in France, Japan, India and Saudi Arabia and subsequently announced the construction of a 90,000 square foot cGMP facility in North Carolina to manufacture vaccines.

Arizona-based VAXX has completed preclinical testing and will soon initiate a human trial of a tobacco-based vaccine for Norwalk norovirus, which causes gastroenteritis in as many as 74M Americans each year. If successful, the company will likely extend its technology to other vaccines.

Like the usage of tobacco plants to cultivate recombinant virus-like particles, some scientists are using insects to circumvent the traditional chicken-egg production process. Research appearing in a January 2010 issue of the Biotechnology Journal from scientists at the University of Natural Resources and Applied Life Science in Vienna, Austria described a new technique for producing H1N1 vaccines using insect cells. The process took just ten weeks to produce H1N1 swine flu cells for subsequent study in mice. The paper noted that immunization with the cells induced high serum antibody titers against A/California/04/2009 as well as hemagglutination inhibiting antibodies for two different insect cell lines, Sf9 and BTI-TN5B1-4 (High Five).

Novavax also infects insect cells with VLPs. The company’s VLPs contain 3 surface antigens (HA, NA and M1) to induce broader, more effective antibodies against disease rather than just the HA antibodies present in most vaccines. In early stage clinical studies of an influenza vaccine, results were favorable with strong immune response and good treatment toleration across thousands of patients in all doses. Novavax is able to prepare the first doses approximately 11 weeks after the receipt of the sequence.

Nanoparticles, defined as very fine particles ranging in size from one to 100 nanometers, are increasingly being used in a variety of medical and other applications as a means to achieve goals that were previously unattainable. The particles are of great scientific interest because their properties are often distinct from those of the larger amounts of the same material. Depending upon the material, these properties include color, melting points, electromagnetic characteristics, etc. In vaccine delivery, some developers are using nano particles to more precisely deliver vaccine payloads. For example, privately-held Liquidia Technologies uses its Particle Replication In Non-Wetting Templates (PRINT) technology to create nanoparticles that can improve the safety and efficacy of injected vaccines, using less antigen without an additional adjuvant. The PRINT Platform creates rationally designed nanoparticles with complete control over particle size, shape, composition and surface chemistry in a controlled and scalable manufacturing process. Each of these variables can be optimized for a specific immunogenic response. For conjugate polysaccharide vaccines, PRINT can simply mold a protein and polysaccharide together in a single particle, improving production. In early 2011, Liquidia announced a collaboration with the PATH Malaria Vaccine Initiative to explore the use of PRINT to design next generation malaria vaccines as well as a $10M investment to support this research by the Bill & Melinda Gates Foundation.

These promising developments in new vaccines and the way they are produced and delivered should make for a robust market opportunity in years to come.